The present invention is concerned with a delayed-pulse release matrix tablet dosage formulation that is characterized by a rapid release of drug during the terminal phase of drug release from a particular tablet. The tablet contains a blend of two different hydroxypropyl cellulose ethers. The combined effect of the selected hydroxypropyl cellulose ethers is to provide a delayed pulse release of an active medicament. The rate of release of the medicament may be controlled by the relative amounts of the different hydroxypropyl cellulose ethers.
In U.S. Pat. No. 4,369,172, which is incorporated by reference, hydroxypropyl methylcellulose having a number average molecular weight (M.sub.n) below 50,000, and a hydroxypropyl content of 9-12 wt. % was disclosed as a carrier base for unit dose of a pharmaceutical which provides a regular and prolonged release pattern for a systemically administered absorbable medicament or active ingredient incorporated therein.
U.S. Pat. No. 4,704,285 discloses sustained release pharmaceutical compositions which are based on the use of finely divided hydroxypropyl cellulose which has at least 50 wt. % of the particles passing through a 100 mesh screen.
U.S. Pat. No. 4,369,172 points out that U.S. Pat. No. 3,065,143 discloses the use of hydroxypropyl methylcelluloses having a viscosity of 4000 and 15000 cps as determined by the method described in ASTM D-2363-72 (2 wt. % aqueous solution at 20.degree. C.)
These hydroxypropyl methylcelluloses have a methoxyl content of 28-30 wt. % and 19-24 wt. % respectively and a hydroxylpropyl content of 7.5-12 wt. % and 4-12 wt. % respectively.
U.S. Pat. No. 4,389,393, which is incorporated by reference, describes the use of a hydroxypropyl methylcellulose as a carrier base for pharmaceutical solid unit dose formulations, wherein the carrier base may also include from 0 to 30 wt. % of methyl cellulose, sodium carboxy methylcellulose or another cellulose ether wherein the carrier base is less than one-third by weight of the solid dosage unit form.
The applicants have discovered that if a tablet prepared from a medicament and two types of hydroxypropyl cellulose having different molecular weights, a pharmaceutical formulation is obtained which has excellent delayed-pulse, sustained release characteristics over at least a 12 hour period.